Controlling protein action Flashcards
What kind of consequences (diseases) can arise as a result of loss of protein control?
- cancer
- haemophilia
- polycytic kidney disease
What is haemophilia?
a genetic deficiency in clotting factor VIII which causes increased bleeding and usually affects males
In what ways can protein interactions be controlled?
- expression and degradation
- interaction domains
- localisation
- ligand binding
- protein switches
- protein modifications
How can protein activity be controlled by expression and degradation?
- control level of lifetime of protein
- can be controlled by level transcription
- level of mRNA and protein can be controlled by regulating degradation
What effect can increasing protein expression have?
Increase rates of reaction
What effect can degrading certain amounts of protein expression have?
Degrading certain proteins can limit rates of reaction
How can effector ligand binding affect protein action?
binding of the ligand molecule induces a conformational change to the protein to either inhibit or activate it.
What kind of ligands control protein action?
Competetive inhibitors - Bind to AS in place of activator molecule
Allosteric regulation- Bind to the allosteric site and induce a conformational change of the AS
How does product feedback inhibition control protein action?
Product inhibition ensures that the activity of an enzyme is reduced when there is sufficient product for the pathway.
How can allosteric regulation lead to activation of proteins?
Ligands binding to a regulatory subunit (allosteric regulation) may lead to them dissociating away from the protein and leave the activated catalytic subunits ready for action.
Eg. Protein kinase A by cAMP
What types of allosteric regulation can control protein action?
Feedback inhibition
Activation
Cooperative binding
How does allosteric regulation aid cooperative binding?
eg. O2 and Hb
As the ligand binds to the allosteric site, It induces a conformational change in the protein so that its AS has a higher affinity for its other ligands and therefore increases the chances of these sites become activated.
How can interaction domains control protein action?
Proteins are often made up of multiple domains ands subunits which interact with a range of mlecules leading to varying actions within a cell.
What examples show interaction domains controlling protein action?
Localisation - DNA recruits other proteins
Scaffold proteins - creat signal hubs
Intramolecular binding - Binding of 2 domains in the same molecule can inhibit enzymatic activity
How can localisation of a protein control its action?
Proteins controlling specific actions will be found in particular locations where they can work most effectively.
Multiple proteins may be colocated if they share a common pathway.
Give examples of localisation controlling protein aciton
Transcription factors will not work in the cytoplasm since DNA is in the nucleus
How can protein switches control protein action?
Some proteins can be switched on or off depending if they are required or not.
What are most protein switches?
Hydrolytic enzymes that hydrolyse nucleotide triphosphates such as GTPases or ATPases.
How do GTPases act as switches?
When carrying out hydrolytic activity they can control intracellular transport, protein synthesis, cell growth.
How do ATPases act as switches?
Act as transporters moving material or motor protein complexes.
How can post translational modifications affect protein action?
Covalent modifications increasing protein/proteome complexity which can be reversible or irreversible
What effects can PMTs have on proteins?
Increase/decrease activity
Localisation
Interaction with other proteins/ligands
Degradation
How does phosphorylation control protein action?
Covalent addition of a phosphate group to serine, threonine or tyrosine residues..
Adds a double negative charge affecting the protein conformations and their interaction activities.
Often used to activate or deactivate protein signalling pathways
What maintains a tight regulation of complex pathways?
feedback control
